Liu Jianyun, Gallo Richard M, Duffy Carol, Brutkiewicz Randy R
1 Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, Indiana.
2 Department of Biological Sciences, University of Alabama , Tuscaloosa, Alabama.
Viral Immunol. 2016 Sep;29(7):409-16. doi: 10.1089/vim.2015.0145. Epub 2016 Jun 21.
CD1d-restricted T (natural killer T [NKT]) cells are important for controlling a herpes simplex virus (HSV) infection. One of the mechanisms of immune evasion by HSV is to downregulate CD1d-mediated activation of NKT cells. VP22 is an HSV-1-encoded protein responsible for reorganizing the host cell's cytoskeletal network and viral spreading. We have previously shown that modification of the cytoskeleton can alter CD1d-mediated antigen presentation. In this study, we found that an HSV-1 lacking VP22 (ΔUL49) was impaired in its ability to inhibit CD1d-mediated antigen presentation compared with the wild-type (WT) virus; this was reversed by a repair virus (UL49R) in CD1d-expressing cells. We further demonstrated that CD1d recycling was inhibited by infection with WT and UL49R, but not the ΔUL49 virus. Ectopic expression of VP22 in CD1d-expressing cells complemented the VP22-deficient virus in inhibiting antigen presentation. Moreover, inhibiting viral protein synthesis rescued VP22-dependent inhibition of CD1d antigen presentation. In conclusion, our findings suggest that VP22 is required (but not sufficient) for the inhibition of CD1d-mediated antigen presentation by an HSV-1 infection.
CD1d限制性T（自然杀伤T [NKT]）细胞对于控制单纯疱疹病毒（HSV）感染很重要。HSV免疫逃逸的机制之一是下调CD1d介导的NKT细胞激活。VP22是一种由HSV-1编码的蛋白质，负责重组宿主细胞的细胞骨架网络和病毒传播。我们之前已经表明，细胞骨架的修饰可以改变CD1d介导的抗原呈递。在本研究中，我们发现与野生型（WT）病毒相比，缺乏VP22的HSV-1（ΔUL49）抑制CD1d介导的抗原呈递的能力受损；在表达CD1d的细胞中，修复病毒（UL49R）可逆转这种情况。我们进一步证明，WT和UL49R感染会抑制CD1d循环，但ΔUL49病毒不会。在表达CD1d的细胞中异位表达VP22可补充VP22缺陷病毒对抗原呈递的抑制作用。此外，抑制病毒蛋白合成可挽救VP22依赖的CD1d抗原呈递抑制。总之，我们的研究结果表明，VP22是HSV-1感染抑制CD1d介导的抗原呈递所必需的（但不充分）。
